This invention relates to novel aminopropylaminobleomycin derivatives.
Bleomycin is a carcinostatic antibiotic discovered in 1966 by Umezawa, one of the present inventors, and his colleagues (Umezawa et al., The Japanese Journal of Antibiotics, page 200, 1966). It is a water-soluble basic glycopeptide which is produced by Streptomyces verticillus, an Actinomycete, and which easily chelates one bivalent copper. This antibiotic that has hitherto been produced by the ordinary cultivation method and isolated includes 16 copper-containing bleomycins (e.g. Umezawa et al., The Japanese Journal of Antibiotics 19A, page 210, 1966). Among these bleomycins are A1, A2, A5, B2, demethyl-A2, etc. that are available as a copper-free mixture (hereinafter referred to as bleomycin complex). Currently, bleomycin complex is widely used in clinical practice to treat cancer, and achieved excellent results in the treatment of squamous cell carcinoma and other types of cancer such as skin cancer, cancer of the head and neck, pulmonary cancer, or malignant lympohoma.
U.S. Pat. Nos. 3,922,262 and Re. 30,451 also disclose various bleomycins.
Bleomycins, however, are markedly restricted in terms of methods to use them and so on, because they produce adverse reactions, such as pulmonary toxicity, depending on the ways of using them.